Clinical Trial 23744

• Overview

  Study Title:

  ACCELERATE: A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients with Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

  Summary:

  The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination.

  Objective:

  ACCEL-001: Primary: The primary objective of this study is to compare GRFS following transplantation of a PBSC product from a MMUD between standard-of-care PTCy-based GVHD prophylaxis (the control arm) and the combination of reduced-dose PTCy, abatacept, and tacrolimus. Secondary: 1. To assess GFS post HCT Additional secondary objectives are the following for each of the treatment arms: 1. To assess IFS post HCT 2. To assess OS-HCT 3. To assess PFS post HCT 4. To assess NRM post HCT 5. To assess the cumulative incidence of relapse and disease progression post HCT 6. To assess the cumulative incidence of neutrophil engraftment post HCT 7. To assess the cumulative incidence of platelet engraftment post HCT 8. To assess PGF and secondary graft failure post HCT 9. To assess the incidence of ≥ grade 2 infections post HCT 10. To assess donor cell engraftment post HCT 11. To assess the cumulative incidence of aGVHD post HCT 12. To assess the cumulative incidence of cGVHD post HCT 13. To assess the incidence of CRS post HCT ACCEL-002: Primary: The primary objective of this study is to compare 1-year GRFS following transplantation of a PBSC product from a MMUD between standard-of-care PTCy-based GVHD prophylaxis (the control arm) and the combination of reduced-dose PTCy, ruxolitinib, tacrolimus, and MMF. Secondary: 1. To assess GFS post HCT Additional secondary objectives are the following for each of the treatment arms: 1. To assess IFS post HCT 2. To assess OS post HCT 3. To assess PFS post HCT 4. To assess NRM post HCT 5. To assess the cumulative incidence of relapse and disease progression post HCT 6. To assess the cumulative incidence of neutrophil engraftment post HCT 7. To assess the cumulative incidence of platelet engraftment post HCT 8. To assess primary graft failure and secondary graft failure post HCT 9. To assess the incidence of ≥ Grade 2 infections post HCT 10. To assess donor cell engraftment post HCT 11. To assess the cumulative incidence of aGVHD post HCT 12. To assess the cumulative incidence of cGVHD post HCT 13. To assess the incidence of CRS post HCT

• Treatments

  Therapies:

  Bone Marrow Transplant; Chemotherapy (NOS); Immunosuppressant; Radiotherapy

  Medications:

  Abatacept (); Alkeran (Melphalan); Cellcept (Mycophenolate Mofetil); FK506 (Tacrolimus); Jakafi (Ruxolitinib); Melphalan (); Mycophenolate Mofetil (); Ruxolitinib (); Tacrolimus (); Total body irradiation (TBI) (); busulfan (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • Age 18 to > Stated willingness to comply with all study procedures and availability for the duration of the study
  • Planned MAC regimen (see protocol for allowed MAC regimens)
  • Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age 16-35
  • Product planned for infusion is MMUD T-cell replete PBSC as allograft
  • HCT-CI > One of the following diagnoses: (1) AML, ALL, or other acute leukemia in first remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extramedullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning. (2) Patients with MDS with no circulating blasts and with > Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results
  • Estimated creatinine clearance ≥ 45mL/min calculated by equation
  • Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin ≥ 50% and forced expiratory volume in first second (FEV1) predicted ≥ 50% based on most recent PFT results
  • Liver function acceptable per local institutional guidelines
  • KPS of ≥ 70% (Appendix I - Performance Status)
  • Other criteria may apply

• Exclusion Criteria

  Exclusion Criteria:
  • Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
  • Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • Subjects with a prior allogeneic transplant
  • Subjects with an autologous transplant within the past 3 months
  • Subjects who are breastfeeding or pregnant
  • Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
  • Concurrent enrollment on a GVHD prevention clinical trial
  • Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant
  • Patients who are HIV-positive with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well-controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.
  • Other exclusions may apply

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